Although the toxic effects of cisplatinum of kidney have been appreciated for some time, the renal handling of cisplatinum and the mechanism by which the renal toxicity occurs are still incompletely understood. These mechanisms could be more easily defined if the molecular sites of interaction of cisplatin were recognized. This project is designed to define how the kidney handles cisplatin under normal conditions and after various pretreatments or other experimental conditions. Inherent in this study is an attempt to localize the sites of interaction of cisplatin and its intracellular binding sites. This section reports the comparative effects of two different diuretic agents on platinum renal toxicity, the effect of regional arterial infusion of cisplatin on platinum levels in target tissues, the potentiation of cisplatin oto- and nephro-toxicity by concomitant administration of aminoglycoside antibiotics, and the animal pharmacokinetics of the cisplatin analog CBDCA and the differentiating agent HMBA.